Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.
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The San Francisco Examiner - Friday, Sept. 5, 1997
Lisa M. Krieger, Examiner Medical Writer
A team from Yale University Medical School announced in Friday's issue of the journal Cell that they have built a strain of virus with the uncanny ability to kill cells infected with HIV, but not healthy bystander cells.
The engineered virus reduced HIV to undetectable levels, raising the possibility of an entirely new kind of therapy for treating AIDS and maybe other viral diseases.
Although the work was done in the lab and is not yet ready to be tried in human patients, "the reports are highly significant as they represent a leap forward in how we might apply basic understandings of viral biology to the design of therapies," wrote Stanford University Medical Center's Dr. Garry P. Nolan in an accompanying editorial.
The creation of anti-virus viruses "boldly demonstrates that it is now possible to reverse the aim of the biochemical grappling hooks that HIV uses to enter cells - and to employ them against the virus itself," according to Nolan.
The approach is exciting because it employs the exact chemical cues that HIV uses, making it difficult for the AIDS virus to sidestep the assault.
Moreover, the highly selective therapy - engineered to go only where it does good, not bad, thus reducing nasty side effects - holds potential for treatment of other diseases, not just AIDS, according to scientists.
"It's like a conversion from traditional bombing to laser-guided smart bombs," Dr. Ronald Desrosiers of the Harvard Medical School told the New York Times. "This virus doesn't seem to infect any cells other than those infected with HIV."
Ironically, the hunter-seeker virus is derived from domesticated versions of an ancient enemy of humans: the rabies virus. This rabies relative, called vesicular stomatitis virus (VSV), is a cattle virus and not lethal to humans.
Scientists first disabled the VSV so it couldn't infect its usual cellular targets.
Then they inserted into the virus some genes for HIV-specific receptors, which are proteins on the surface of immune system cells that permit entry and infection by the AIDS virus.
Working from this new set of instructions, the chimeric virus then sought out, entered and killed human cells that showed signs of hidden HIV infection.
"This is a classic case of predator-prey population dynamics at the molecular level," according to Nolan.
Remarkably, the engineered virus even replicates in cells - becoming, in a sense, a live therapy that is capable of multiplying and proliferating, not only killing bad cells but then moving on to kill others.
The VSV, created by Dr. John K. Rose of Yale, ultimately cut HIV production more than 300-fold to levels that were barely detectable or undetectable.
A similar approach using a modified rabies virus to attack HIV-infected cells has been developed at the Federal Research Center for Virus Diseases of Animals in Tuebingen, Germany, and is also reported in Friday's Cell. But this rabies virus does not kill the infected cells.
At this early point in the research, it is premature to introduce the new viruses into humans, even if intended for good purposes, noted Nolan.
This is because the new viruses might affect the health of an immunocompromised patient. They might spread to unintended cells or be transferred, accidentally, to ther people.
The regulatory authorities at the federal Food and Drug Administration, among others, are likely to raise their eyebrows at the prospect of viral therapy.
The next hurdle is for the therapy to be tried in animals, in this case monkeys infected with the monkey version of HIV, known as simian immunodeficiency virus or SIV.
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